School of Biomedical Sciences, University of Queensland, St Lucia, Qld 4072, Australia

The release of growth hormone (GH) in
mammals occurs in a pulsatile manner, which is critical for its
physiological functions: essential during early puberty and growth, and crucial
in maintaining metabolic balance during adulthood. Hypothalamic GH releasing
hormone (GHRH) and somatostatin maintain the pulsatile release of GH. Metabolic
regulatory hormones, ghrelin, leptin and insulin, also regulate GH pulsatile release
from pituitary somatotrophs.

In mouse, GH pulsatile patterns from early-puberty (5
weeks) to post-puberty age (10 weeks) become more regular and less frequent without
total GH difference. In early-adulthood (12-16 weeks), GH pulsatile and total secretions
are reduced with increase in age. To characterize the impact of dietary induced
weight gain (DIWG) and increased adiposity on the post-pubertal decline of GH in
mice, pulsatile GH secretion at 12 and 16 weeks of age in normal and 4-8 weeks of high fat feeding (HFF) was analyzed showing reduced GH secretion. In addition to GH, circulating levels of leptin, insulin, glucose,
free fatty acids, and liver triglycerides at 16 weeks were also assessed. HFF resulted in an increase in adiposity and leptin levels, liver
triglycerides, glucose intolerance and hyper-insulineamia. Pulsatile GH profile in
HFF 12 weeks of age was similar to that in normal feeding 16 weeks. It is also
evidenced that reduction in GH pulsatile release occurred even before weight
gain or HFF but correlated closely with body adipose tissues.

Observations suggest that GH pulsatile regulation
is established in early puberty time and amplitudes of pulse are reduced along
age after puberty; this post-puberty decline in GH is facilitated by DIWG with increased
adiposity in mice. Further, reduced GH secretion occurs before DIWG indicating
causative role to obesity. Given the established role of GH on post-pubertal
somatic development, we anticipate that reduced GH secretion with dietary induced
weight gain and increased adiposity will have long-term ramifications on adult
health and ageing process.